Outlaw Murals

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Reported self-control is not meaningfully associated with inhibition-related executive function:A Bayesian analysis

Self-control is assessed using a remarkable array of measures. In a series of five data-sets (overall N = 2,641) and a mini meta-analysis, we explored the association between canonical operationalisations of self-control: The Self-Control Scale and two measures of inhibition-related executive functioning (the Stroop and Flanker paradigms). Overall, Bayesian correlational analyses suggested little-to-no relationship between self-reported self-control and performance on the Stroop and Flanker tasks. The Bayesian meta-analytical summary of all five data-sets further favoured a null relationship between both types of measurement. These results suggest that the field’s most widely used measure of self-reported self-control is uncorrelated with two of the most widely adopted executive functioning measures of self-control. Consequently, theoretical and practical conclusions drawn using one measure (e.g., the Self-Control Scale) cannot be generalised to findings using the other (e.g., the Stroop task). The lack of empirical correlation between measures of self-control do not invalidate either measure, but instead suggest that treatments of the construct of self-control need to pay greater attention to convergent validity among the many measures used to operationalize self-control

Intention-oriented programming support for runtime adaptive autonomic cloud-based applications

The continuing high rate of advances in information and communication systems technology creates many new commercial opportunities but also engenders a range of new technical challenges around maximising systems' dependability, availability, adaptability, and auditability. These challenges are under active research, with notable progress made in the support for dependable software design and management. Runtime support, however, is still in its infancy and requires further research. This paper focuses on a requirements model for the runtime execution and control of an intention-oriented Cloud-Based Application. Thus, a novel requirements modelling process referred to as Provision, Assurance and Auditing, and an associated framework are defined and developed where a given system's non/functional requirements are modelled in terms of intentions and encoded in a standard open mark-up language. An autonomic intention-oriented programming model, using the Neptune language, then handles its deployment and execution. © 2013 Elsevier Ltd. All rights reserved

Syntheses of Ir 4 (CO) 6 (η 5 -C 5 Me 4 H) 2 and Ir 7 (μ 3 -CO) 3 (CO) 12 (η 5 -C 5 Me 5 ) from Pentametallic Molybdenum-Iridium Cluster Precursors.

Reaction of Mo2Ir3(μ-CO)3(CO)6(η5-C5H5)2(η5-C5Me5) with Ir(CO)2(η5-C5Me4H) afforded the four-valence-electron-deficien

Three-dimensional electron microscopy reveals the evolution of glomerular barrier injury

Open access articleGlomeruli are highly sophisticated filters and glomerular disease is the leading cause of kidney failure. Morphological change in glomerular podocytes and the underlying basement membrane are frequently observed in disease, irrespective of the underlying molecular etiology. Standard electron microscopy techniques have enabled the identification and classification of glomerular diseases based on two-dimensional information, however complex three-dimensional ultrastructural relationships between cells and their extracellular matrix cannot be easily resolved with this approach. We employed serial block face-scanning electron microscopy to investigate Alport syndrome, the commonest monogenic glomerular disease, and compared findings to other genetic mouse models of glomerular disease (Myo1e−/−, Ptpro−/−). These analyses revealed the evolution of basement membrane and cellular defects through the progression of glomerular injury. Specifically we identified sub-podocyte expansions of the basement membrane with both cellular and matrix gene defects and found a corresponding reduction in podocyte foot process number. Furthermore, we discovered novel podocyte protrusions invading into the glomerular basement membrane in disease and these occurred frequently in expanded regions of basement membrane. These findings provide new insights into mechanisms of glomerular barrier dysfunction and suggest that common cell-matrix-adhesion pathways are involved in the progression of disease regardless of the primary insult

Is Dissonance Reduction a Special Case of Fluid Compensation? Evidence That Dissonant Cognitions Cause Compensatory Affirmation and Abstraction

Cognitive dissonance theory shares much in common with other perspectives that address anomalies, uncertainty, and general expectancy violations. This has led some theorists to argue that these theories represent overlapping psychological processes. If responding to dissonance and uncertainty occurs through a common psychological process, one should expect that the behavioral outcomes of feeling uncertain would also apply to feelings of dissonance, and vice versa. One specific prediction from the meaning maintenance model would be that cognitive dissonance, like other expectancy violations, should lead to the affirmation of unrelated beliefs, or the abstraction of unrelated schemas when the dissonant event cannot be easily accommodated. This article presents 4 studies (N ϭ 1124) demonstrating that the classic induced-compliance dissonance paradigm can lead not only to a change of attitudes (dissonance reduction), but also to (a) an increased reported belief in God (Study 2), (b) a desire to punish norm-violators (Study 1 and 3), (c) a motivation to detect patterns amid noise (Study 3), and (d) polarizing support of public policies among those already biased toward a particular side (Study 4). These results are congruent with theories that propose content-general fluid compensation following the experience of anomaly, a finding not predicted by dissonance theory. The results suggest that dissonance reduction behaviors may share psychological processes described by other theories addressing violations of expectations

Basement membrane ligands initiate distinct signalling networks to direct cell shape

Cells have evolved mechanisms to sense the composition of their adhesive microenvironment. Although much is known about general mechanisms employed by adhesion receptors to relay signals between the extracellular environment and the cytoskeleton, the nuances of ligand-specific signalling remain undefined. Here, we investigated how glomerular podocytes, and four other basement membrane-associated cell types, respond morphologically to different basement membrane ligands. We defined the composition of the respective adhesion complexes using mass spectrometry-based proteomics. On type IV collagen, all epithelial cell types adopted a round morphology, with a single lamellipodium and large adhesion complexes rich in actin-binding proteins. On laminin (511 or 521), all cell types attached to a similar degree but were polygonal in shape with small adhesion complexes enriched in endocytic and microtubule-binding proteins. Consistent with their distinctive morphologies, cells on type IV collagen exhibited high Rac1 activity, while those on laminin had elevated PKCα. Perturbation of PKCα was able to interchange morphology consistent with a key role for this pathway in matrix ligand-specific signalling. Therefore, this study defines the switchable basement membrane adhesome and highlights two key signalling pathways within the systems that determine distinct cell morphologies. Proteomic data are availableviaProteomeXchange with identifier PXD017913

Global analysis reveals the complexity of the human glomerular extracellular matrix.

The glomerulus contains unique cellular and extracellular matrix (ECM) components, which are required for intact barrier function. Studies of the cellular components have helped to build understanding of glomerular disease; however, the full composition and regulation of glomerular ECM remains poorly understood. We used mass spectrometry-based proteomics of enriched ECM extracts for a global analysis of human glomerular ECM in vivo and identified a tissue-specific proteome of 144 structural and regulatory ECM proteins. This catalog includes all previously identified glomerular components plus many new and abundant components. Relative protein quantification showed a dominance of collagen IV, collagen I, and laminin isoforms in the glomerular ECM together with abundant collagen VI and TINAGL1. Protein network analysis enabled the creation of a glomerular ECM interactome, which revealed a core of highly connected structural components. More than one half of the glomerular ECM proteome was validated using colocalization studies and data from the Human Protein Atlas. This study yields the greatest number of ECM proteins relative to previous investigations of whole glomerular extracts, highlighting the importance of sample enrichment. It also shows that the composition of glomerular ECM is far more complex than previously appreciated and suggests that many more ECM components may contribute to glomerular development and disease processes. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000456

High-nuclearity ruthenium carbonyl cluster chemistry. 9. Ligand substitution at decaruthenium carbonyl clusters

The mono- to tri-substituted decaruthenium cluster anions [Ru10(μ-H)(μ6-C)(CO)24-x(L)x]- [L = P(C6H4Me-4)3, AsPh3, SbPh3, x = 1-3] were prepared as their [PPh4]+ salts in moderate to good yields from reaction of [PPh4][Ru10(μ-H)(μ6-C)(CO)24] with the corresponding group 15 ligands at room temperature in acetone. The tetrakis-substituted cluster Ru10(μ6-C)(μ3-CO)(μ-CO)(CO)19(P(C6H4Me-4)3)4 was obtained in high yield from [PPh4]2[Ru10(μ6-C)(CO)24] and an excess of the phosphine under the same conditions; a single-crystal X-ray diffraction study revealed that the phosphines ligate at the vertices of the "giant tetrahedral" core. Kinetics studies of the formation of [PPh4][Ru10(μ-H)(μ6-C)(AsPh3)2(CO)22] from [PPh4][Ru10(μ-H)(μ6-C)(AsPh3)(CO)23] shows that ligand substitution at these giant tetrahedral clusters proceeds via a strongly associative pathway with the likely intermediacy of a Ru-Ru bond-cleaved intermediat

SET-PP2A complex as a new therapeutic target in KMT2A (MLL) rearranged AML

© 2023, The Author(s). The version of record of this article, first published in [Oncogene], is available online at Publisher’s website: http://dx.doi.org/10.1038/s41388-023-02840-1KMT2A-rearranged (KMT2A-R) is an aggressive and chemo-refractory acute leukemia which mostly affects children. Transcriptomics-based characterization and chemical interrogation identified kinases as key drivers of survival and drug resistance in KMT2A-R leukemia. In contrast, the contribution and regulation of phosphatases is unknown. In this study we uncover the essential role and underlying mechanisms of SET, the endogenous inhibitor of Ser/Thr phosphatase PP2A, in KMT2A-R-leukemia. Investigation of SET expression in acute myeloid leukemia (AML) samples demonstrated that SET is overexpressed, and elevated expression of SET is correlated with poor prognosis and with the expression of MEIS and HOXA genes in AML patients. Silencing SET specifically abolished the clonogenic ability of KMT2A-R leukemic cells and the transcription of KMT2A targets genes HOXA9 and HOXA10. Subsequent mechanistic investigations showed that SET interacts with both KMT2A wild type and fusion proteins, and it is recruited to the HOXA10 promoter. Pharmacological inhibition of SET by FTY720 disrupted SET-PP2A interaction leading to cell cycle arrest and increased sensitivity to chemotherapy in KMT2A-R-leukemic models. Phospho-proteomic analyses revealed that FTY720 reduced the activity of kinases regulated by PP2A, including ERK1, GSK3β, AURB and PLK1 and led to suppression of MYC, supporting the hypothesis of a feedback loop among PP2A, AURB, PLK1, MYC, and SET. Our findings illustrate that SET is a novel player in KMT2A-R leukemia and they provide evidence that SET antagonism could serve as a novel strategy to treat this aggressive leukemia. [Abstract copyright: © 2023. The Author(s).